July 20, 2012

First Genetic Sequence Of Individual Human Sperm

Sperm cells can look the same with a similar tadpole appearance. However, the cells showcase differences among the genes. Recently, researchers were able to capture an image of the varieties among genes which they say is particularly helpful in understanding the genome and male fertility.

The research is featured in the July 20 edition of Cell, a Cell Press journal. The scientists believe that the methods used could help researchers better understand male reproductive disorders. The findings also demonstrate how human genes are changed in the process of passing on human genetic material. The coded information, located in the sperm and egg, becomes more diversified to produce different features.

"We have developed single-cell genome analysis technologies that enabled us to characterize how any given person mixes together their paternal and maternal inheritances to create potential offspring," explained first author Jianbin Wang, a graduate student in the Department of Bioengineering at Stanford University, in a prepared statement.

The research team, led by Professor Stephen Quake at Stanford University and the Howard Hughes Medical Institute, worked on getting genome maps from 91 single sperm cells of a 40-year-old man who had healthy children. They created a personal map of the DNA within his sperm and captured an image of the new mutations that formed within each sperm cell as the DNA changed to create more genetic diversity. The technology featured in the article is more advanced than what´s currently available to map human population and provides a detailed map for individuals.

"Application of this technology could significantly enhance our understanding of reproductive disorders. In addition, it may be paradigm shifting with respect to sperm or egg selection for in vitro fertilization," remarked coauthor Dr. Barry Behr, professor of obstetrics and gynecology and director of Stanford's in vitro fertilization laboratory, in the statement.

The Stanford Study demonstrated how previous estimates based on population were pretty accurate. The sperm in a sample underwent an approximate average of 23 recombinations or mixing events. Individual sperm had a different number of genetic mixing and genetic mutations that would come about.

"For the first time, we were able to generate an individual recombination map and mutation rate for each of several sperm from one person," remarked Behr in the statement. "Now we can look at a particular individual, make some calls about what they would likely contribute genetically to an embryo and perhaps even diagnose or detect potential problems."

Cells generally have “diploids,” which are two copies of 23 chromosomes. Recombination happens during meiosis, where a chromosome splits into a sperm in males and eggs in females. A fertilized egg is produced when a sperm and egg combine together.

"The exact sites, frequency and degree of this genetic mixing process is unique for each sperm and egg cell," noted Quake in the statement, "and we've never before been able to see it with this level of detail. It's very interesting that what happens in one person's body mirrors the population average."

The scientists believe that the study is the first to have a whole-genome sequence of a human gamete, which is the cells that pass on parents´ physical traits and eventually develop into a child.

"This represents the culmination of nearly a decade of work in my lab," explained Quake in the statement. "We now have devices that will allow us to routinely amplify and sequence to a high degree of accuracy the entire genomes of single cells, which has far-ranging implications for the study of cancer, infertility and many other disorders."

The research also advances current technology of sequencing sperm cells based on recombination, a natural process that produces a blend of DNA from the child´s four grandparents.

"Single-sperm sequencing will allow us to chart and understand how recombination differs between individuals at the finest scales. This is an important proof of principle that will allow us to study both fundamental dynamics of recombination in humans and whether it is involved in issues relating to male infertility," remarked Gilean McVean, an unaffiliated professor of statistical genetics at the Wellcome Trust Centre for Human Genetics, in the statement.

Lastly, researchers will also gain valuable information on how male fertility and the changes in sperm quality tend to increase as people become older.

"This could serve as a new kind of early detection system for men who may have reproductive problems," concluded Behr, who also co-directs Stanford's reproductive endocrinology and infertility program, in the statement. "It's also possible that we could one day use other, correlating features to harmlessly identify healthy sperm for use in IVF. In the end, the DNA is the raw material that ultimately defines a sperm's potential. If we can learn more about this process, we can better understand human fertility."